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Protein Modules in Signal Transduction pp 325–342Cite as

Signaling Through Grb2/Ash-Control of the Ras Pathway and Cytoskeleton

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Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 228))

Abstract

Src homology regions (SH) are recognized as a conserved sequence among non-receptor protein tyrosine kinases (PTK), including v-Src, v-Abl, and v-Fps (Sadowski et al. 1986). Besides the kinase domain (termed SH1), SH comprises two independent modular units, SH2 and SH3, and has been found in a variety of proteins that quite often contain both SH2 and SH3 domains (Cohen et al. 1995; Pawson 1995). These proteins can be categorized broadly into two, groups: (1) molecules that themselves have enzymatic activity, such as phospholipase Cγ, Src family tyrosine kinases and ras GTPase-activating protein(GAP); and (2) proteins that lack a catalytic domain but contain only the SH domains and other signaling modules, such as Nek, c-Crk, She and the phosphoinositide 3-kinase 85-kDa subunit (PI3 K p85). Members of the latter group are often referred to as “adaptors.” The interaction between SH2 domains and tyrosine-phosphorylated proteins is important in the assembly of signal transduction complexes. On the other hand, SH3 domains recognize proline-rich sequences, thereby signaling downstream targets. Adaptors containing SH2 and SH3 domains form signaling machines in themselves. Grb2/Ash is one such adaptor. This molecule has already been established to be important in the intracellular signal transduction system, as reviewed by Downward (1994) and Chardin et al. (1995), but many laboratories are still accumulating evidence for its pivotal and indispensable roles in a variety of cell regulatory processes.

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Authors and Affiliations

  1. Department of Biochemistry, Institute of Medical Science, University of Tokyo, Shirokanedai, Minatoku, Tokyo 108, Japan

    T. Takenawa & H. Miki

  2. Department of Biosignaling, Tokyo Metropolitan Institute of Gerontology, Sakae-cho, Itabashi-ku, Tokyo 173, Japan

    K. Matuoka

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  2. H. Miki
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  3. K. Matuoka
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  1. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, M5G 1X5, Toronto, Ontario, Canada

    Anthony J. Pawson FRS

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© 1998 Springer-Verlag Berlin Heidelberg

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Takenawa, T., Miki, H., Matuoka, K. (1998). Signaling Through Grb2/Ash-Control of the Ras Pathway and Cytoskeleton. In: Pawson, A.J. (eds) Protein Modules in Signal Transduction. Current Topics in Microbiology and Immunology, vol 228. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-80481-6_12

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  • DOI: https://doi.org/10.1007/978-3-642-80481-6_12

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-80483-0

  • Online ISBN: 978-3-642-80481-6

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